title: Target-specific mechanics of phagocytosis: protrusive neutrophil response to zymosan differs from the uptake of antibody-tagged pathogens.
abstract: The physical mechanisms that control target-specific responses of human neutrophils to distinct immune threats are poorly understood. Using dual-micropipette manipulation, we have quantified and compared the time courses of neutrophil phagocytosis of two different targets: zymosan (a prominent model of fungal infection), and antibody-coated (Fc) particles. Our single-live-cell/single-target approach exposes surprising differences between these two forms of phagocytosis. Unlike the efficient uptake of 3-μm Fc targets (within ~66 seconds), the engulfment of similarly sized zymosan is slow (~167 seconds), mainly due to the formation of a characteristic pedestal that initially pushes the particle outwards by ~1 μm. Despite a roughly twofold difference in maximum cortical tensions, the top 'pull-in' speeds of zymosan and Fc targets are indistinguishable at ~33 nm/second. Drug inhibition shows that both actin as well as myosin II partake in the regulation of neutrophil cortical tension and cytoplasmic viscosity; other than that, myosin II appears to play a minor role in both forms of phagocytosis. Remarkably, an intact actin cytoskeleton is required to suppress, in antibody-mediated phagocytosis, the initially protrusive deformation that distinguishes the neutrophil response to zymosan.
authors.affiliation: Department of Biomedical Engineering, University of California Davis, Davis, CA 95616, USA.
authors.forename: Cheng-Yuk
authors.initials: CY
authors.lastname: Lee
authors.forename: Marc
authors.initials: M
authors.lastname: Herant
authors.forename: Volkmar
authors.initials: V
authors.lastname: Heinrich
mesh_terms: D000199:Actins / Q000276:immunology; D000906:Antibodies / Q000276:immunology*; D001696:Biomechanical Phenomena; D002465:Cell Movement; D002478:Cells, Cultured; D005658:Fungi / Q000276:immunology / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009181:Mycoses / Q000276:immunology* / Q000382:microbiology; D024462:Myosin Type II / Q000276:immunology; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D010587:Phagocytosis; D015054:Zymosan / Q000276:immunology*
chemical_list: D000199:Actins; D000906:Antibodies; D015054:Zymosan; D024462:Myosin Type II